Adult-born granule cells mature through two functionally distinct states

  1. János Brunner
  2. Máté Neubrandt
  3. Susan Van-Weert
  4. Tibor Andrási
  5. Felix B Kleine Borgmann
  6. Sebastian Jessberger
  7. János Szabadics  Is a corresponding author
  1. Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary
  2. University of Zurich, Switzerland

Abstract

Adult-born granule cells (ABGCs) are involved in certain forms of hippocampus-dependent learning and memory. It has been proposed that young but functionally integrated ABGCs (4-weeks-old) specifically contribute to pattern separation functions of the dentate gyrus due to their heightened excitability, whereas old ABGCs (>8-weeks-old) lose these capabilities. Measuring multiple cellular and integrative characteristics of 3-10 weeks old individual ABGCs, we show that ABGCs consist of two functionally distinguishable populations showing highly distinct input integration properties (one group being highly sensitive to narrow input intensity ranges while the other group linearly reports input strength) that are largely independent of the cellular age and maturation stage, suggesting that 'classmate' cells (born during the same period) can contribute to the network with fundamentally different functions. Thus, ABGCs provide two temporally overlapping but functionally distinct neuronal cell populations, adding a novel level of complexity to our understanding of how life-long neurogenesis contributes to adult brain function.

Article and author information

Author details

  1. János Brunner

    Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  2. Máté Neubrandt

    Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  3. Susan Van-Weert

    Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  4. Tibor Andrási

    Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  5. Felix B Kleine Borgmann

    University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Sebastian Jessberger

    University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. János Szabadics

    Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    For correspondence
    szabadics.janos@koki.mta.hu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Gary L Westbrook, Vollum Institute, United States

Ethics

Animal experimentation: All experimental procedures were performed in accordance with the ethical guidelines of the Institute of Experimental Medicine Protection of Research Subjects Committee (permission: 22.1/1760/003/2009) and were approved by the local virus safety committee.

Version history

  1. Received: April 16, 2014
  2. Accepted: July 23, 2014
  3. Accepted Manuscript published: July 24, 2014 (version 1)
  4. Version of Record published: August 13, 2014 (version 2)

Copyright

© 2014, Brunner et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,284
    views
  • 332
    downloads
  • 33
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. János Brunner
  2. Máté Neubrandt
  3. Susan Van-Weert
  4. Tibor Andrási
  5. Felix B Kleine Borgmann
  6. Sebastian Jessberger
  7. János Szabadics
(2014)
Adult-born granule cells mature through two functionally distinct states
eLife 3:e03104.
https://doi.org/10.7554/eLife.03104

Share this article

https://doi.org/10.7554/eLife.03104

Further reading

    1. Neuroscience
    Alexandra L Jellinger, Rebecca L Suthard ... Steve Ramirez
    Research Article

    Negative memories engage a brain and body-wide stress response in humans that can alter cognition and behavior. Prolonged stress responses induce maladaptive cellular, circuit, and systems-level changes that can lead to pathological brain states and corresponding disorders in which mood and memory are affected. However, it is unclear if repeated activation of cells processing negative memories induces similar phenotypes in mice. In this study, we used an activity-dependent tagging method to access neuronal ensembles and assess their molecular characteristics. Sequencing memory engrams in mice revealed that positive (male-to-female exposure) and negative (foot shock) cells upregulated genes linked to anti- and pro-inflammatory responses, respectively. To investigate the impact of persistent activation of negative engrams, we chemogenetically activated them in the ventral hippocampus over 3 months and conducted anxiety and memory-related tests. Negative engram activation increased anxiety behaviors in both 6- and 14-month-old mice, reduced spatial working memory in older mice, impaired fear extinction in younger mice, and heightened fear generalization in both age groups. Immunohistochemistry revealed changes in microglial and astrocytic structure and number in the hippocampus. In summary, repeated activation of negative memories induces lasting cellular and behavioral abnormalities in mice, offering insights into the negative effects of chronic negative thinking-like behaviors on human health.

    1. Neuroscience
    Alexandra H Leighton, Juliette E Cheyne, Christian Lohmann
    Research Article

    Synaptic inputs to cortical neurons are highly structured in adult sensory systems, such that neighboring synapses along dendrites are activated by similar stimuli. This organization of synaptic inputs, called synaptic clustering, is required for high-fidelity signal processing, and clustered synapses can already be observed before eye opening. However, how clustered inputs emerge during development is unknown. Here, we employed concurrent in vivo whole-cell patch-clamp and dendritic calcium imaging to map spontaneous synaptic inputs to dendrites of layer 2/3 neurons in the mouse primary visual cortex during the second postnatal week until eye opening. We found that the number of functional synapses and the frequency of transmission events increase several fold during this developmental period. At the beginning of the second postnatal week, synapses assemble specifically in confined dendritic segments, whereas other segments are devoid of synapses. By the end of the second postnatal week, just before eye opening, dendrites are almost entirely covered by domains of co-active synapses. Finally, co-activity with their neighbor synapses correlates with synaptic stabilization and potentiation. Thus, clustered synapses form in distinct functional domains presumably to equip dendrites with computational modules for high-capacity sensory processing when the eyes open.